FDA Grants Orphan Drug Designation to BOLD-100 for Gastric Cancer

The FDA has granted an orphan drug designation to the first-in-class ruthenium-based small molecule therapeutic BOLD-100 for the treatment of patients with gastric cancer.

The FDA has granted an orphan drug designation to the first-in-class ruthenium-based small molecule therapeutic BOLD-100 for the treatment of patients with gastric cancer, according to an announcement from Bold Therapeutics, the drug developer.1

BOLD-100 was designed to modify the unfolded protein response through selective GRP78 inhibition and to elicit reactive oxygen species which results in DNA damage and cell cycle arrest; this all leads to cell death in both sensitive and resistant cancers.

Due to this, the agent has the potential to substantially improve outcomes across a wide array of solid and liquid tumors and to be paired with other anticancer agents, ranging from traditional chemotherapies to novel targeted options.

“We are pleased that the FDA granted BOLD-100 an orphan drug designation in the treatment of gastric cancer, adding to our existing orphan drug designation in pancreatic cancer,” Jim Pankovich, EVP, clinical development at Bold Therapeutics, stated in a press release. “Data submitted in the orphan drug application demonstrated that BOLD-100 is potentially effective against this deadly cancer.”

In the phase 1b BOLD-100-001 trial (NCT04221820; TRIO039), investigators are examining BOLD-100 in combination with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) for the treatment of patients with gastric, pancreatic, colorectal, and bile duct cancers.2 The study will include a dose-escalation cohort (part A) to ensure safety and tolerability; this will then be followed by a dose-expansion phase (part B).

To be eligible for enrollment, patients need to be at least 18 years of age, have previously treated histologically and/or cytologically confirmed metastatic or unresectable selected gastrointestinal (GI) tumor, have measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 to 1, and acceptable organ function.3

If patients had neuropathy that was greater than grade 2 in severity, were intolerant or had a reaction to fluorouracil or oxaliplatin, had a history or presence of central nervous system metastases or leptomeningeal tumors, had active cardiac disease or a history of cardiac dysfunction, or had GI tract disease with malabsorption syndrome, they were excluded.

For part A of the trial, patients need to have received at least 1 prior line of chemotherapy in the metastatic setting. For Part B, the setting will depend on the GI tumor. For those with colorectal, pancreatic, and bile duct cancers, patients must have previously received 1 line of therapy. Patients with bile duct cancer specifically need to have received at least 1 gemcitabine-based regimen. For patients with gastric cancer, those who had not received prior treatment could still participate.

Part A of the trial will screen 25 to 30 patients to enroll up to 20 participants with either gastric, pancreatic, colorectal, or bile duct cancer. Patients will receive dose level 1 of the combination and then go on to either dose level 2 and dose level 3 or dose level -1 and if not tolerated, end of the study. Treatment will be administered until either disease progression or unacceptable toxicity.

For part B, investigators anticipate enrolling up to 80 patients, with a maximum of 25 patients per treatment arm. Arm 1 will include patients with gastric cancer who are receiving first-line treatment and arm 2 will include those with gastric cancer who are receiving treatment in the second line. Moreover, arms 3, 4, and 5 will receive the combination in the second line for pancreatic, colorectal, and bile duct cancers, respectively. In this phase of the trial, patients will receive BOLD-100 at the recommended dose plus FOLFOX until either progressive disease, intolerable toxicity, or study withdrawal. Radiological assessments will be done every 2 months.

The primary objective of part A is safety and tolerability, as well as to define the maximum-tolerated dose of the agent. For part B, the primary end point is to evaluate the efficacy of the combination with regard to progression-free survival, overall survival, and response rate. Secondary objectives include pharmacokinetic and pharmacodynamic parameters, as well as exploring potential biomarkers that may be predictive of efficacy with the approach.

“Importantly, we continue to gather additional data on BOLD-100 from our ongoing phase 1b trial in the treatment of advanced gastric, pancreatic, colorectal, and bile duct cancers and anticipate applying for one more breakthrough therapy designation for BOLD-100 as clinical efficacy data become available,” Pankovich added in the release.

The phase 1b trial continues to enroll patients at 6 sites across Canada: Cross Cancer Institute, Ottawa General Hospital, Jewish General Hospital, and Royal Victoria Hospital. The work is expected to transition into a phase 2 trial later in 2021, with additional clinical sites to be added in both the United States and Korea, according to the pharmaceutical company.


  1. FDA grants Bold Therapeutics’ BOLD-100 an orphan drug designation (ODD) in the treatment of gastric cancer. News release. Bold Therapeutics Inc. May 11, 2021. Accessed May 11, 2021. https://prn.to/3vYI2Bi
  2. BOLD-100 in combination with FOLFOX for the treatment of advanced solid tumors. ClinicalTrials.gov. Updated October 22, 2020. Accessed May 11, 2021. https://clinicaltrials.gov/ct2/show/NCT04421820
  3. O’Kane GM, Spratlin JL, Kavan P, et al. BOLD-100-001 (TRIO039): a phase 1b dose-escalation study of BOLD-100 in combination with FOLFOX chemotherapy in patietns with advanced gastrointestinal solid tumors. J Clin Oncol. 2021;39(suppl 3):TPS145. doi:10.1200/JCO.2021.39.5_suppl.TPS145